This proposal describes a 5 year training program for the development of an academic career in Geriatrics with a research focus on the basic Biology of Aging. The principal investigator has completed clinical training in Geriatrics and is now pursuing essentially full-time research using the free-living nematode, C. elegans, to study the genetic regulation of aging and lifespan determination. The training program consists of structured didactic work and mentored research experiences designed to build upon the principle investigator's prior research experience in the areas of DNA binding proteins, transcriptional regulation, and fruitfly, Drosophila, genetics. Specifically the program will develop new research abilities in the areas of Biology of Aging, C. elegans genetics, and Bioinformatics/Genomics. The proposal also includes a research program which seeks to advance the understanding of aging through study of the worm. Specifically, study will focus on the orphan nuclear hormone receptor daf-12. Target genes for this receptor are predicted to have important roles in regulating the aging of the worm. The timing of daf-12 in regulating lifespan will initially determined, and then target genes directly regulated by daf- 12 during this window of action will be isolated by using DNA microarrays with confirmation of direct regulation by chromatin immunoprecipitation. Isolated target genes will be characterized with respect to their roles in aging and responses to environmental stressors, such as heat, oxidative stress, bacterial pathogens, and UV radiation. The goal of these studies will be to identify new genes with roles in aging and develop the tools needed to ultimately understand the biochemical and molecular functions of these genes. The ultimate goal of the training program is to allow the principal investigator to develop a program in the basic Biology of Aging within a Geriatrics Division. An improved understanding of the biochemical events involved in aging and the responses of an organism to these events will greatly enhance our understanding of the aging process and the link between aging and disease. This understanding holds the potential for the development of treatments to address the negative consequences of aging or to prevent diseases associated with aging. Additionally, an improved understanding of the aging process will provide insight into the differences between geriatric patients and younger patients especially with regards to differences in disease symptoms and response to treatments.